Lipid Metabolism-related Genes Research Articles

Identification and validation of lipid metabolism-related key genes as novel biomarkers in acute myocardial infarction and pan-cancer analysis.

Acute myocardial infarction (AMI) is associated with high morbidity and mortality, and is associated with abnormal lipid metabolism. We identified lipid metabolism related genes as biomarkers of AMI, and explored their mechanisms of action. Microarray datasets were downloaded from the GEO database and lipid metabolism related genes were obtained from Molecular Signatures Database. WGCNA was performed to identify key genes. We evaluated differential expression and performed ROC and ELISA analyses. We also explored the mechanism of AMI mediated by key genes using gene enrichment analysis. Finally, immune infiltration and pan-cancer analyses were performed for the identified key genes. TRL2, S100A9, and HCK were identified as key genes related to lipid metabolism in AMI. Internal and external validation (including ELISA) showed that these were good biomarkers of AMI. In addition, the results of gene enrichment analysis showed that the key genes were enriched in inflammatory response, immune system process, and tumor-related pathways. Finally, the results of immune infiltration showed that key genes were concentrated in neutrophils and macrophages, and pan-cancer analysis showed that the key genes were highly expressed in most tumors and were associated with poor prognosis. TLR2, S100A9, and HCK were identified as lipid metabolism related novel diagnostic biomarkers of AMI. In addition, AMI and tumors may be related through the inflammatory immune response.

Combination of UGT1A1 polymorphism and baseline plasma bilirubin levels in predicting the risk of antipsychotic-induced dyslipidemia in schizophrenia patients.

The prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia. The present study included 644 schizophrenia patients from two centers. Demographic and clinical characteristics were collected at baseline and 4 weeks after admission to investigate the correlation between metabolites, episodes, usage of AAPDs, and occurrence of dyslipidemia. Besides, we explored the combined predictive value of genotypes and baseline bilirubin for dyslipidemia by employing multiple PCR targeted capture techniques to sequence two pathways: bilirubin metabolism-related genes and lipid metabolism-related genes. Our results indicated that there existed a negative correlation between the changes in bilirubin levels and triglyceride (TG) levels in patients with schizophrenia. Among three types of bilirubin, direct bilirubin in the baseline (DBIL-bl) proved to be the most effective in predicting dyslipidemia in the ROC analysis (AUC = 0.627, p < 0.001). Furthermore, the odds ratio from multinomial logistic regression analysis showed that UGT1A1*6 was a protective factor for dyslipidemia (ß = -12.868, p < 0.001). The combination of baseline DBIL and UGT1A1*6 significantly improved the performance in predicting dyslipidemia (AUC = 0.939, p < 0.001). Schizophrenia patients with UGT1A1*6 mutation and a certain level of baseline bilirubin may be more resistant to dyslipidemia and have more selections for AAPD than other patients.

Exercise influences fatty acids in the longissimus dorsi muscle of Sunit lambs and improves dressing percentage by affecting digestion, absorption, and lipid metabolism

The transition from grazing to captive rearing resulted in a significant decline in meat quality. To enhance the quality of meat from captive sheep, we examined the impact of exercise on Sunit lambs. The lambs, with similar body weight and aged 3 months underwent a 90-day period of thought-driven exercise. At the end of the exercise period, we collected colonic contents, epithelial tissues, and the longissimus dorsi muscle, and recorded slaughter performance. Exercise was found to have a significant impact on the content of short-chain fatty acids in the colon. Additionally, it generally reduced the mRNA expression of fatty acid absorption transporter genes in the colonic epithelium and lipid metabolism-related genes in the longissimus dorsi muscle. Furthermore, exercise significantly affected the content of fatty acids in the longissimus dorsi muscle of Sunit lambs, and increased its dressing percentage. Exercise influences the composition of fatty acids of the longissimus dorsi muscle and improves dressing percentage by affecting the digestion, absorption, and metabolism of lipids in Sunit lambs. This could be profitable for the livestock industry, and could alter the nutrition and flavor of lamb meat.

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes

Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3ʹ UTR and four miRNAs were identified through in silico assays. The aim of this study is to verify the binding ability of the four miRNAs to the SNPs within the 3ʹUTR of GPAM, and to identify the regulatory function of miR-375 in the expression of genes related to lipid metabolism in mammalian adipocytes. It was verified that the four miRNAs bind to the GPAM 3ʹUTR, and identified that the miR-375 sequence is highly conserved. Furthermore, it was founded that miR-375 upregulated the GPAM gene, C/EBPα, PPARγ and lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.

Retraction Note: Integration of clinical and spatial data to explore lipid metabolism-related genes for predicting prognosis and immune microenvironment in gliomas.

Retraction Note: Integration of clinical and spatial data to explore lipid metabolism-related genes for predicting prognosis and immune microenvironment in gliomas.

Dietary kelp meal improves serum antioxidants, intestinal immunity, and lipid metabolism in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).

Dietary kelp possesses a variety of useful biological qualities but does not have a toxic effect on the host. In this study, we examine how kelp dietary supplementation enhances the serum biochemistry, intestinal immunity, and metabolism of hybrid snakehead. A total of 810 juvenile hybrid snakeheads (Channa maculata ♀ × Channa argus ♂), with an initial average weight of 11.4 ± 0.15 g, were allocated randomly to three treatment groups (three replicates per group). The fish were fed for 60 days with isonitrogenous and isolipidic diets. The groups were the control group (C) (20% high-gluten flour), the medium replacement group (MR) (10% high-gluten flour and 10% kelp meal), and the full replacement group (FR) (0% high-gluten flour and 15% kelp meal). The results showed that dietary kelp increased the activity of serum antioxidant enzymes significantly and decreased the content of serum malondialdehyde (MDA) in hybrid snakeheads, with significant changes in the FR group (P < 0.05). The intestinal morphology results showed that dietary kelp helped to increase the specific surface area of intestinal villi, which was beneficial for intestinal digestion and absorption. According to transcriptome and quantitative real-time polymerase chain reaction (qRT-PCR) analysis, dietary kelp can improve the expression of intestinal immunity and metabolism-related pathways. Among them, immune-related genes MHC1 and HSPA1 were significantly up-regulated, and IGH, MHC2, and IL-8 were significantly down-regulated (P < 0.05). Lipid metabolism-related genes DGAT2, FABP2, RXRα, and PLPP1 were all significantly up-regulated (P < 0.05). Dietary kelp can effectively improve the antioxidant function of hybrid snakeheads, improve intestinal morphology, reduce intestinal inflammation, and promote intestinal lipid synthesis and transportation, thereby improving intestinal immunity and metabolic functions. © 2024 Society of Chemical Industry.

Correlation study of serum lipid levels and lipid metabolism-related genes in cervical cancer.

Lipid metabolism plays an important role in cancer. The aim of this study was to investigate the relationship between lipid metabolism and the development of cervical cancer, and to explore the prognostic significance of lipid metabolism-related genes in patients with cervical cancer. Initially, we retrospectively collected data from 1589 cervical cancer patients treated at the Affiliated Hospital of Qingdao University, with 1589 healthy individuals from the physical examination center serving as the control group. The correlation between their serum lipid levels and cervical cancer was analyzed. Subsequently, leveraging public databases, we conducted comprehensive studies on lipid metabolism-related genes. Additionally, we analyzed RNA expression profiling and clinical information sourced from TCGA and GTEx databases. Finally, we established a prognostic model integrating 9 genes associated with lipid metabolism and generated a nomogram model using R. GO and KEGG were performed to explore the functions and pathways of lipid metabolism-related genes. Our findings revealed that patients with cervical cancer exhibited dyslipidemia, characterized by elevated levels of TC, TG, and LDL-C, alongside reduced HDL-C levels compared to controls (P<0.05). Interestingly, compared with early-stage patients, advanced patients had lower HDL-C level and higher LDL-C level. Regression analysis further highlighted high TC, TG, and LDL-C as significant risk factors for cervical cancer. Then a total of 188 lipid metabolism-related genes were identified and a prognostic signature based on 9 genes was established and validated. The results of the GO and KEGG functional analysis indicated that the lipid metabolism-related genes are primarily concentrated on pathways associated with fatty acid metabolism. Our study underscores the varying degrees of dyslipidemia observed in patients with cervical cancer, emphasizing the relevance of serum lipids in disease development. Our prognostic riskScore model predicted the overall survival time of patients based on 9 genes associated with lipid metabolism. These 9 genes may be tumor biomarkers and new targets for the treatment of cervical cancer.

Network pharmacology combined with molecular docking and molecular dynamic simulation to reveal the potential mechanism of lentinan ameliorating hyperlipidemia

Hyperlipidemia is closely related to multiple diseases and is characterized by abnormal serum lipid profiles. The biological function of lentinan in mice and rats was studied, but the mechanism of its lipid-lowering effect was not completely clear. In this study, network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the potential mechanism of its lipid-lowering effect and high-fat diet (HFD) mice was used to confirm the predicted mechanism. Our results indicated that lentinan could ameliorate hyperlipidemia by regulating peroxisome proliferator-activated receptors (PPARs), sterol response element-binding protein-1 (SREBP1), and nuclear factor kappa-B (NF-κB) in the hepatic tissues of mices. Further animal experiment showed that lentinan could regulate the mRNA expressions of lipid metabolism-related genes, such as PPARα, PPARδ, PPARγ, cluster of differentiation 36 (CD36) and SREBP-1c. Moreover, lentinan supplementation could reduce the expressions of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide sythase (iNOS). In cell model, lentinan also could inhibit oleic acid-induced lipid droplet formation and the expressions of lipid metabolism-related genes and reduced inflammatory factor expressions in HepG2 cells, which further approved the results of animal experiment. Taken together, our results suggest that lentinan can ameliorate hyperlipidemia via regulating lipid metabolism-related gene expressions and reduce obesity-induced inflammatory response.

Glycometabolism and lipid metabolism related genes predict the prognosis of endometrial carcinoma and their effects on tumor cells

BackgroundGlycometabolism and lipid metabolism are critical in cancer metabolic reprogramming. The primary aim of this study was to develop a prognostic model incorporating glycometabolism and lipid metabolism-related genes (GLRGs) for accurate prognosis assessment in patients with endometrial carcinoma (EC).MethodsData on gene expression and clinical details were obtained from publicly accessible databases. GLRGs were obtained from the Genecards database. Through nonnegative matrix factorization (NMF) clustering, molecular groupings with various GLRG expression patterns were identified. LASSO Cox regression analysis was employed to create a prognostic model. Use rich algorithms such as GSEA, GSVA, xCELL ssGSEA, EPIC,CIBERSORT, MCPcounter, ESTIMATE, TIMER, TIDE, and Oncoppredict to analyze functional pathway characteristics of the forecast signal, immune status, anti-tumor therapy, etc. The expression was assessed using Western blot and quantitative real-time PCR techniques. A total of 113 algorithm combinations were combined to screen out the most significant GLRGs in the signature for in vitro experimental verification, such as colony formation, EdU cell proliferation, wound healing, apoptosis, and Transwell assays.ResultsA total of 714 GLRGs were found, and 227 of them were identified as prognostic-related genes. And ten GLRGs (AUP1, ESR1, ERLIN2, ASS1, OGDH, BCKDHB, SLC16A1, HK2, LPCAT1 and PGR-AS1) were identified to construct the prognostic model of patients with EC. Based on GLRGs, the risk model’s prognosis and independent prognostic value were established. The signature of GLRGs exhibited a robust correlation with the infiltration of immune cells and the sensitivity to drugs. In cytological experiments, we selected HK2 as candidate gene to verify its value in the occurrence and development of EC. Western blot and qRT-PCR revealed that HK2 was substantially expressed in EC cells. According to in vitro experiments, HK2 knockdown can increase EC cell apoptosis while suppressing EC cell migration, invasion, and proliferation.ConclusionThe GLRGs signature constructed in this study demonstrated significant prognostic value for patients with endometrial carcinoma, thereby providing valuable guidance for treatment decisions.

Cervical cancer subtype identification and model building based on lipid metabolism and post-infection microenvironment immune landscape

BackgroundAs the second most common gynecological cancer, cervical cancer (CC) seriously threatens women's health. The poor prognosis of CC is closely related to the post-infection microenvironment (PIM). This study investigated how lipid metabolism-related genes (LMRGs) affect CC PIM and their role in diagnosing CC. MethodsWe analyzed lipid metabolism scores in the CC single-cell landscape by AUCell. The differentiation trajectory of epithelial cells to cancer cells was revealed using LMRGs and Monocle2. Consensus clustering was used to identify novel subgroups using the LMRGs. Multiple immune assessment methods were used to evaluate the immune landscape of the subgroups. Prognostic genes were determined by the LASSO and multivariate Cox regression analysis. Finally, we perform molecular docking of prognostic genes to explore potential therapeutic agents. ResultsWe revealed the differentiation trajectory of epithelial cells to cancer cells in CC by LMRGs. The higher LMRGs expression cluster had higher survival rates and immune infiltration expression. Functional enrichment showed that two clusters were mainly involved in immune response regulation. A novel LMR signature (LMR.sig) was constructed to predict clinical outcomes in CC. The expression of prognostic genes was correlated with the PIM immune landscape. Small molecular compounds with the best binding effect to prognostic genes were obtained by molecular docking, which may be used as new targeted therapeutic drugs. ConclusionWe found that the subtype with better prognosis could regulate the expression of some critical genes through more frequent lipid metabolic reprogramming, thus affecting the maturation and migration of dendritic cells (DCs) and the expression of M1 macrophages, reshaping the immunosuppressive environment of PIM in CC patients. LMRGs are closely related to the PIM immune landscape and can accurately predict tumor prognosis. These results further our understanding of the underlying mechanisms of LMRGs in CC.

Development of a Novel Lipid Metabolism-related Gene Prognostic Signature for Patients with Colorectal Cancer.

The purpose of this study was to explore the expression profiles of lipid metabolism-related genes in patients with Colorectal Cancer (CRC). The lipid metabolism statuses of CRC patients from The Cancer Genome Atlas (TCGA) were analyzed. Risk characteristics were constructed by univariate Cox regression and minimum Absolute contraction and Selection Operator (LASSO) Cox regression. A histogram was constructed based on factors such as age, sex, TNM stage, T stage, N stage, and risk score to provide a visual tool for clinicians to predict the probability of 1-year, 3-year, and 5-year OS for CRC patients. By determining Area Under Curve (AUC) values, the time-dependent Receiver Operating characteristic Curve (ROC) was used to evaluate the efficiency of our model in predicting prognosis. A novel risk signal based on lipid metabolism-related genes was constructed to predict the survival of CRC patients. Risk characteristics were shown to be an independent prognostic factor in CRC patients (p <0.001). There were significant differences in the abundance and immune characteristics of tumor-filtering immune cells between high-risk and low-risk groups. The nomogram had a high potential for clinical application and the ROC AUC value was 0.827. Moreover, ROC analysis demonstrated that the nomogram model was more accurate to predict the survival of CRC patients than age, gender, stage and risk score. In this study, we demonstrated a lipid metabolism-related genes prognosis biomarker associated with the tumor immune micro-environment in patients with CRC.

Identification of potential key lipid metabolism-related genes involved in tubular injury in diabetic kidney disease by bioinformatics analysis.

Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD.

Dietary lipid supplementation alleviated the impacts of polystyrene nanoplastic exposure in Litopenaeus vannamei

The widespread occurrence of nanoplastic (NP) pollution in the environment is a growing concern, and its presence poses a potential threat to cultured aquatic animals. Previously, we found that NPs can significantly affect the lipid metabolism of shrimp. However, relevant reports about the effects of increasing dietary lipid levels on NP toxicity are lacking. Therefore, we explored the effects of dietary supplementation with different lipid levels on the growth and lipid metabolism of Pacific white shrimp (Litopenaeus vannamei). We cultured L. vannamei at three dietary lipid levels (3 %, 6 %, and 9 %) and three NP concentrations (0, 1, and 3 mg/L) for 2 months. We evaluated the effects of lipid levels on growth indexes, hepatopancreas morphological structure, lipid metabolism-related enzyme activity, and gene expression of the shrimp. The results showed that as lipid intake increased, the survival rate, body weight growth rate, and hepatosomatic ratio of the shrimp increased while the feed conversion rate decreased. Additionally, the crude protein and crude lipid contents increased, whereas the moisture and ash contents did not change much. We found that the morphological structure of the hepatopancreas was seriously damaged in the 3 mg/L NPs and 3 % dietary lipid group. Finally, lipid metabolism-related enzyme activities and gene expression levels increased with increased dietary lipid levels. Together, these results suggest that increasing dietary lipid content can improve shrimp growth and alleviate lipid metabolism disorders caused by NPs. This study is the first to show that nutrition regulation can alleviate the toxicity of NPs, and it provides a theoretical basis for the green and healthy culture of L. vannamei.

Transcriptome Analysis of mfs2-Defective Penicillium digitatum Mutant to Reveal Importance of Pdmfs2 in Developing Fungal Prochloraz Resistance.

Demethylation inhibitors (DMIs), including prochloraz, are popular fungicides to control citrus postharvest pathogens such as Penicillium digitatum (green mold). However, many P. digitatum strains have developed prochloraz resistance, which decreases drug efficacy. Specific major facilitator superfamily (MFS) transporter gene mfs2, encoding drug-efflux pump protein MFS2, has been identified in P. digitatum strain F6 (PdF6) to confer fungal strain prochloraz resistance. However, except for the drug-efflux pump function of MFS2, other mechanisms relating to the Pdmfs2 are not fully clear. The present study reported a transcriptome investigation on the mfs2-defective P. digitatum strain. Comparing to the wild-type strain, the mfs2-defective strain showed 717 differentially expressed genes (DEGs) without prochloraz induction, and 1221 DEGs with prochloraz induction. The obtained DEGs included multiple isoforms of MFS transporter-encoding genes, ATP-binding cassette (ABC) transporter-encoding genes, and multidrug and toxic compound extrusion (MATE) family protein-encoding genes. Many of these putative drug-efflux pump protein-encoding genes had significantly lower transcript abundances in the mfs2-defective P. digitatum strain at prochloraz induction, as compared to the wild-type strain, including twenty-two MFS transporter-encoding genes (MFS1 to MFS22), two ABC transporter-encoding genes (ABC1 and ABC2), and three MATE protein-encoding genes (MATE1 to MATE3). The prochloraz induction on special drug-efflux pump protein genes in the wild-type strain was not observed in the mfs2-defective strain, including MFS21, MFS22, ABC2, MATE1, MATE2, and MATE3. On the other hand, the up-regulation of other drug-efflux pump protein genes in the mfs2-defective strain cannot recover the fungal prochloraz resistance, including MFS23, MFS26, MFS27, MFS31, MFS33, and ABC3 to ABC8. The functional enrichment of DEGs based on Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and euKaryotic Orthologous Groups (KOG) database resources suggested some essential contributors to the mfs2-relating prochloraz resistance, including ribosome biosynthesis-related genes, oxidative phosphorylation genes, steroid biosynthesis-related genes, fatty acid and lipid metabolism-related genes, and carbon- and nitrogen-metabolism-related genes. The results indicated that the MFS2 transporter might be involved in the regulation of multiple drug-efflux pump protein gene expressions and multiple metabolism-related gene expressions, thus playing an important role in developing P. digitatum prochloraz resistance.

Dietary Lycium barbarum Polysaccharide Modulates Growth Performance, Antioxidant Capacity, and Lipid Metabolism in Common Carp (Cyprinus carpio) Fed with High-Fat Diet.

To investigate the ameliorative effects and mechanism of Lycium barbarum polysaccharide (LBP) on growth performance, oxidative stress, and lipid deposition in common carp (Cyprinus carpio) fed with high-fat diets, fish with an initial weight of 5.29 ± 0.12 g were divided into five experimental groups-including normal-fat diets, high-fat diets, and high-fat diets-supplemented with LBP (0.5, 1.0, and 2.0 g/kg) for 8 weeks. The results showed that high-fat diets resulted in significant decreases in final body weight, weight gain rate, and specific growth rate of fish, as well as causing a significant decrease in hepatic total antioxidant capacity, catalase, and glutathione peroxidase activities. These changes were accompanied by a significant decrease in lipase activity and ATP level and a significant increase in malondialdehyde content. The expression levels of lipid metabolism-related genes (acetyl coenzyme A carboxylase 1, stearoyl coenzyme A desaturase 1, fat synthase, peroxisome proliferator-activated receptor-γ, fructofuranose bisphosphatase, and glucose-6-phosphatase) were also markedly elevated by high-fat diets. Supplementation with 0.5-2.0 g/kg LBP in high-fat diets improved the reduced growth performance, increased hepatic total antioxidant enzymes, catalase, and glutathione peroxidase activities, and lowered malondialdehyde level in fish fed with high-fat diets. Additionally, dietary supplementation with LBP significantly downregulated hepatic gene expression levels of acetyl coenzyme A carboxylase 1, stearoyl coenzyme A desaturase 1, fat synthase, sterol regulatory element-binding protein 1, peroxisome proliferator-activated receptor-γ, fructofuranose bisphosphatase, and glucose-6-phosphatase. In conclusion, fish fed with high-fat diets demonstrated impaired growth performance, antioxidant capacity, and lipid metabolism, and dietary supplementation with 0.5-2.0 g/kg LBP ameliorated the impairments induced by high-fat diets.

Lipid Deficiency Contributes to Impaired Alveolar Progenitor Cell Function in Aging and Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated interstitial lung disease resulting from repeated epithelial injury and inadequate epithelial repair. Alveolar type II cells (AEC2) are progenitor cells that maintain epithelial homeostasis and repair the lung after injury. In the current study, we assessed lipid metabolism in AEC2s from human lungs of IPF patients and healthy donors, as well as AEC2s from bleomycin-injured young and old mice. Through single cell RNA sequencing (scRNA-seq), we observed that lipid metabolism-related genes were downregulated in IPF AEC2s and bleomycin-injured mouse AEC2s. Aging aggravated this decrease and hindered recovery of lipid metabolism gene expression in AEC2s after bleomycin injury. Pathway analyses revealed down-regulation of genes related to lipid biosynthesis and fatty acid -oxidation in AEC2s from IPF lungs and bleomycin-injured, aged mouse lungs compared to the respective controls. We confirmed decreased cellular lipid content in AEC2s from IPF lungs and bleomycin-injured, aged mouse lungs using immunofluorescence staining and flow cytometry. We further show that lipid metabolism was associated with AEC2 progenitor function. Lipid supplementation and peroxisome proliferator activated receptor gamma (PPARγ) activation promoted progenitor renewal capacity of both human and mouse AEC2s in 3D organoid cultures. Lipid supplementation also increased AEC2 proliferation and expression of SFTPC in AEC2s. In summary, we identified a lipid metabolism deficiency in AEC2s from lungs of patients with IPF and bleomycin-injured aged mice. Restoration of lipid metabolism homeostasis in AEC2s might promote AEC2 progenitor function and offer new opportunities for therapeutic approaches to IPF.

Tolypocladium sinense Mycelium Polysaccharide Alleviates Obesity, Lipid Metabolism Disorder, and Inflammation Caused by High Fat Diet via Improving Intestinal Barrier and Modulating Gut Microbiota.

Tolypocladium sinense is a fungus isolated from Cordyceps. Cordyceps has some medicinal value and is also a daily health care product. This study explores the preventive effects of T. sinense mycelium polysaccharide (TSMP) on high-fat diet-induced obesity and chronic inflammation in mice. Here, the study establishes an obese mouse model induced by high-fat diet. In this study, the mice are administered TSMP daily basis to evaluate its effect on alleviating obesity. The results show that TSMP can significantly inhibit obesity and alleviate dyslipidemia by regulating the expression of lipid metabolism-related genes such as liver kinase B1 (LKB1), phosphorylated AMP-activated protein kinase (pAMPK), peroxisome proliferator activated receptor α (PPARα),fatty acid synthase (FAS), and hydroxymethylglutaryl-CoA reductase (HMGCR) in the liver. TSMP can increase the protein expression of zona occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon, improve the intestinal barrier dysfunction, and reduce the level of serum LPS, thereby reducing the inflammatory response. 16S rDNA sequencing shows that TSMP alters the intestinal microbiota by increasing the relative abundance of Akkermansia, Lactobacillus, and Prevotellaceae_NK3B31_group, while decreasing the relative abundance of Faecalibaculum. The findings show that TSMP can inhibit obesity and alleviates obesity-related lipid metabolism disorders, inflammatory responses, and oxidative stress by modulating the gut microbiota and improving intestinal barrier.

Identification and validation of biomarkers related to lipid metabolism in osteoarthritis based on machine learning algorithms

BackgroundOsteoarthritis and lipid metabolism are strongly associated, although the precise targets and regulatory mechanisms are unknown.MethodsOsteoarthritis gene expression profiles were acquired from the GEO database, while lipid metabolism-related genes (LMRGs) were sourced from the MigSB database. An intersection was conducted between these datasets to extract gene expression for subsequent differential analysis. Following this, functional analyses were performed on the differentially expressed genes (DEGs). Subsequently, machine learning was applied to identify hub genes associated with lipid metabolism in osteoarthritis. Immune-infiltration analysis was performed using CIBERSORT, and external datasets were employed to validate the expression of these hub genes.ResultsNine DEGs associated with lipid metabolism in osteoarthritis were identified. UGCG and ESYT1, which are hub genes involved in lipid metabolism in osteoarthritis, were identified through the utilization of three machine learning algorithms. Analysis of the validation dataset revealed downregulation of UGCG in the experimental group compared to the normal group and upregulation of ESYT1 in the experimental group compared to the normal group.ConclusionsUGCG and ESYT1 were considered as hub LMRGs in the development of osteoarthritis, which were regarded as candidate diagnostic markers. The effects are worth expected in the early diagnosis and treatment of osteoarthritis.

Has-miR-199a-3p/RELA/SCD inhibits immune checkpoints in AMD and promotes macrophage-mediated inflammation and pathological angiogenesis through lipid metabolism pathway: A computational analysis.

More and more evidence shows that abnormal lipid metabolism leads to immune system dysfunction in AMD and promotes the occurrence of AMD by changing the homeostasis of ocular inflammation. However, the molecular mechanism underlying the effect of lipid metabolism on the phenotype and function of macrophages is still unclear, and the mechanism of association between AMD and cancer and COVID-19 has not been reported. The purpose of this study is to explore the interaction between lipid metabolism related genes, ferroptosis related genes and immunity in AMD, find out the key genes that affect the ferroptosis of AMD through lipid metabolism pathway and the molecular mechanism that mediates the action of macrophages, and find out the possible mechanism of lipid metabolism and potential co-therapeutic targets between AMD and cancer and COVID-19, so as to improve treatment decision-making and clinical results. For the first time, we have comprehensively analyzed the fatty acid molecule related genes, ferroptosis related genes and immune microenvironment of AMD patients, and determined that mast cells and M1 macrophages are the main causes of AMD inflammation, and found that SCD is the core gene in AMD that inhibits ferroptosis through lipid metabolism pathway, and verified the difference in the expression of SCD in AMD in a separate external data set. Based on the analysis of the mechanism of action of the SCD gene, we found for the first time that Has-miR-199a-3p/RELA/SCD is the core axis of action of lipid metabolism pathway to inhibit the ferroptosis of AMD. By inhibiting the immune checkpoint, we can enhance the immune cell activity of AMD and lead to the transformation of macrophages from M2 to M1, thereby promoting the inflammation and pathological angiogenesis of AMD. At the same time, we found that ACOX2 and PECR, as genes for fatty acid metabolism, may regulate the expression of SCD during the occurrence and development of COVID-19, thus affecting the occurrence and development of AMD. We found that FASD1 may be a key gene for the joint action of AMD and COVID-19, and SCD regulates the immune infiltration of macrophages in glioma and germ line tumors. In conclusion, our results can provide theoretical basis for the pathogenesis of AMD, help guide the treatment of AMD patients and their potentially related diseases and help to design effective drug targets.

Maternal PFOS exposure in mice induces hepatic lipid accumulation and inflammation in adult female offspring: Involvement of microbiome-gut-liver axis and autophagy

Perfluorooctane sulfonates (PFOS) are the persistent organic pollutants. In the present study, 0, 0.3, or 3-mg/kg PFOS were administered to pregnant mice from GD 11 to GD 18. The histopathology of liver and intestine, serum and hepatic lipid levels, lipid metabolism related genes, and gut microbiota were examined in adult female offspring. The results suggested that maternal PFOS exposure increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and induced F4/80+ macrophage infiltration in adult female offspring, in addition to the elevation of TNF-α and IL-1β mRNA levels in low-dose and high-dose groups, respectively. Furthermore, maternal exposure to PFOS increased serum triglyceride (TG) and hepatic total cholesterol (TC) levels, which was associated with the alteration of the process of fatty acid transport and β-oxidation, TG synthesis and transport, cholesterol synthesis and excretion in the liver. The AMPK/mTOR/autophagy signaling was also inhibited in the liver of adult female offspring. Moreover, changes in gut microbiota were also related to lipid metabolism, especially for the Desulfovibrio, Ligilactobacillus, Enterorhabdus, HT002 and Peptococcaceae_unclassified. Additionally, maternal exposure to PFOS decreased mRNA expressions of the tight junction protein and AB+ goblet cells in the colon, while increasing the overproduction of lipopolysaccharides (LPS) and F4/80+ macrophage infiltration. Collectively, maternal PFOS exposure induced liver lipid accumulation and inflammation, which strongly correlated with the disruption of the gut-liver axis and autophagy in adult female offspring, highlighting the persistent adverse effects in offspring exposed to PFOS.